Increasing evidence suggests that cAMP plays an important role in the neuronal functions. The hydrolysis of cAMP to 5'-AMP by phosphodiesterase is the only known mechanism by which the action of cAMP is terminated. Factors affecting the enzymic activities regulate the extent and duration of the action of the cyclic nucleotide. The metabolism and/or function of cAMP appears intertwined with Ca2 ion, but the mechanism linking the two messengers is poorly understood. Calmodulin, a Ca2 ion-binding protein modulator of adenylate cyclase, phosphodiesterase and other enzyme systems, may provide a molecular link between the two messengers. Our objectives are two-fold: 1. to characterize phosphodiesterase from bovine brain with emphasis on its regulatory properties, multiple forms and subunit structures, and 2. to determine if calmodul regulates cellular reactions other than cAMP metabolism in the brain. The latter includes studes on the subcellular localization of calmodul in using immunocytochemical techniques and the identification of calmodulin-binding proteins using conventional biochemical techniques as well as bifunctional crosslinking reagents.